The ribonucleoprotein complex telomerase has been implicated in the establishment and progression of many different types of tumors. Telomerase activity is detected in roughly 80 percent of all tumor cell types, but is absent in most normal cells. Thus, the disruption of telomerase activity is a particularly attractive means for treating multiple types of cancer. Gemini Technologies Inc. is developing a novel class of chimeric oligonucleotides for use in antisense therapeutic strategies. These chimeras are comprised of a standard antisense component, which directs the compound to complementary RNA sequences, and an activator moiety, 2?,5?-oligoadenylate (2-5A) that serve to activate a cellular enzyme, ribonuclease L (RNase L), which cleaves the targeted RNA. Preliminary studies have shown that a 2-5A antisense compound that targets telomerase RNA for degradation inhibits the growth and tumorigenicity of ovarian carcinoma cells in vitro. The goals of the proposed studies are to progress this compound toward commercialization by increasing its stability, affinity for target RINA, and anti-tumor potential through incorporation of stabilizing base modifications. If successful, the 2-5A anti-telomerase compound will have widespread application to the treatment of many tumor types. These studies will also impact other antisense products under development by improving the effectiveness of the 2-A antisense technology.